J&J bags first nod for multiple myeloma bispecific to complement its own CAR-T offering

Johnson & Johnson and partner Legend Biotech already sell BCMA-targeted CAR-T therapy Carvykti. Now, the pharma giant has complemented that complex therapy with an off-the-shelf option.

Teclistamab, a BCMAxCD3 bispecific antibody, has won its first global nod in Europe to treat relapsed and refractory multiple myeloma after at least three prior therapies, J&J said Wednesday. In Europe, the company will sell the med under the brand name Tecvayli.

The European Commission handed out the conditional approval following the European Medicines Agency’s endorsement under the PRIME scheme. The program is designed to speed the regulatory process for medicines that target unmet medical needs with less comprehensive data than is typically required.

Teclistamab works by redirecting CD3-positive T cells to myeloma cells that express BCMA to kill off the cancer cells.

After a median follow-up of 14.1 months in the phase 1/2 MajesTEC-1 trial, teclistama shrank tumors in 63% of 165 heavily pretreated patients who had received at least three—and a median of five—prior lines of therapy. A complete response or better was seen in 39.4% of patients. The patients went a median 11.3 months without disease progression, and they lived for a median 18.3 months.

Tecvayli’s EU nod in fourth-line multiple myeloma matches that of J&J and Legend’s BCMA-directed CAR-T drug Carvykti and of Bristol Myers Squibb’s rival CAR-T Abecma. The three compare favorably to the fifth-line nod GSK got in Europe for its BCMA-targeted antibody-drug conjugate Blenrep.

But while Carvykti and Abecma require complicated and lengthy manufacturing process to re-engineer a patient’s own cells, Tecvayli comes as a ready-to-use, under-the-skin injection.

“Teclistamab has the potential to provide substantial clinical benefit and new hope to these patients, with high rates of deep and durable responses, and the added convenience of being off-the-shelf,” Maria-Victoria Mateos, M.D., Ph.D., from the University Hospital of Salamanca, said in a statement Wednesday. Mateos is also an investigator in MajesTEC-1.

Bispecific antibody drugs like teclistamab have lately become a growing threat to CAR-T drugs. A few weeks ago, Roche got a conditional EU green light for Lunsumio, a CD20xCD3 bispecific, to treat follicular lymphoma. As an off-the-shelf drug, Lunsumio could challenge CD19-directed CAR-T therapies like Gilead Sciences’ Yescarta and Novartis’ Kymriah.

While European regulators have rolled out the red carpet for teclistamab, the FDA appears to be processing J&J’s application slower. J&J’s Janssen submitted teclistamab to the FDA at the end of 2021 before filing to the EMA in January. In an email to Fierce Pharma, a J&J spokesperson restated the company’s policy of not disclosing FDA target action dates but said it continues to work with U.S. regulators on teclistamab.

Teclistamab and Carvykti add to J&J’s growing multiple myeloma portfolio, which also includes blockbuster anti-CD38 antibody Darzalex. In addition, J&J has also reported positive early-phase data for GPRC5DxCD3 bispecific talquetamab in heavily pretreated myeloma patients. Darzalex, teclistamab and talquetamab all incorporate antibody technology from Genmab.

Late-line treatment is obviously not where J&J aims to end up. Hoping to move up in the myeloma treatment order, J&J is pairing teclistamab with Darzalex in the phase 3 MajesTEC-3 trial in patients who have received one to three prior lines of therapy.